Department of Molecular Biomedicine, Developmental Biology of the Immune System, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
Front Immunol. 2024 Jul 22;15:1375528. doi: 10.3389/fimmu.2024.1375528. eCollection 2024.
Tissue-resident macrophages (TRMs) are an integral part of the innate immune system, but their biology is not well understood in the context of cancer. Distinctive resident macrophage populations are identified in different organs in mice using fate mapping studies. They develop from the yolk sac and self-maintain themselves lifelong in specific tissular niches. Similarly, breast-resident macrophages are part of the mammary gland microenvironment. They reside in the breast adipose tissue stroma and close to the ductal epithelium and help in morphogenesis. In breast cancer, TRMs may promote disease progression and metastasis; however, precise mechanisms have not been elucidated. TRMs interact intimately with recruited macrophages, cytotoxic T cells, and other immune cells along with cancer cells, deciding further immunosuppressive or cytotoxic pathways. Moreover, triple-negative breast cancer (TNBC), which is generally associated with poor outcomes, can harbor specific TRM phenotypes. The influence of TRMs on adipose tissue stroma of the mammary gland also contributes to tumor progression. The complex crosstalk between TRMs with T cells, stroma, and breast cancer cells can establish a cascade of downstream events, understanding which can offer new insight for drug discovery and upcoming treatment choices. This review aims to acknowledge the previous research done in this regard while exploring existing research gaps and the future therapeutic potential of TRMs as a combination or single agent in breast cancer.
组织驻留巨噬细胞（TRMs）是先天免疫系统的重要组成部分，但它们在癌症背景下的生物学特性尚未得到很好的理解。通过命运图谱研究，在小鼠的不同器官中鉴定出了独特的驻留巨噬细胞群体。它们起源于卵黄囊，并在特定的组织龛位中自我维持终身。同样，乳腺驻留巨噬细胞是乳腺微环境的一部分。它们存在于乳腺脂肪组织基质中，靠近导管上皮，并有助于形态发生。在乳腺癌中，TRMs 可能促进疾病进展和转移；然而，确切的机制尚未阐明。TRMs 与募集的巨噬细胞、细胞毒性 T 细胞和其他免疫细胞以及癌细胞密切相互作用，决定了进一步的免疫抑制或细胞毒性途径。此外，通常与不良预后相关的三阴性乳腺癌（TNBC）可以具有特定的 TRM 表型。TRMs 对乳腺脂肪组织基质的影响也促进了肿瘤的进展。TRMs 与 T 细胞、基质和乳腺癌细胞之间的复杂串扰可以建立一系列下游事件，了解这些事件可以为药物发现和即将到来的治疗选择提供新的见解。本综述旨在承认这方面的先前研究，同时探讨现有的研究空白和 TRMs 作为联合或单一药物在乳腺癌中的未来治疗潜力。
